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Frontiers in Endocrinology 2024To determine whether the late-follicular-phase progesterone to retrieved oocytes (P/O) ratio during fertilization (IVF)/intracytoplasmic sperm injection (ICSI) impacts...
The late-follicular-phase progesterone to retrieved oocytes ratio in normal ovarian responders treated with an antagonist protocol can be used as an index for selecting an embryo transfer strategy and predicting the success rate: a retrospective large-scale study.
OBJECTIVE
To determine whether the late-follicular-phase progesterone to retrieved oocytes (P/O) ratio during fertilization (IVF)/intracytoplasmic sperm injection (ICSI) impacts pregnancy outcomes.
DESIGN
12,874 cycles were retrospectively categorized into four groups according to the P/O ratio percentile, with divisions at the 25th, 50th and 75th percentiles.
RESULTS
The clinical pregnancy and live birth rates of fresh cycle embryos in Group D were significantly lower than those in the other three groups (45.1% and 39.0%, 43.2% and 37.2%, 39.6% and 33.5%, 33.4% and 28.2% in Group A, B, C, D, respectively; both P < 0.008). Multivariate logistic regression analysis revealed a significant negative correlation between the P/O ratio and live birth, particularly when the P/O ratio was ≥0.22 (OR = 0.862, 95% CI [0.774-0.959], P = 0.006).
CONCLUSIONS
The P/O ratio has certain predictive value for IVF/ICSI pregnancy outcomes and can be used for decision-making decision regarding fresh embryo transfer.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Progesterone; Adult; Embryo Transfer; Ovulation Induction; Fertilization in Vitro; Pregnancy Rate; Oocytes; Oocyte Retrieval; Sperm Injections, Intracytoplasmic; Follicular Phase; Pregnancy Outcome
PubMed: 38812812
DOI: 10.3389/fendo.2024.1338683 -
Turkish Journal of Medical Sciences 2024The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer.
BACKGROUND/AIM
The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer.
MATERIALS AND METHODS
A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child.
RESULTS
The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed.
CONCLUSION
Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.
Topics: Humans; Female; Breast Neoplasms; Breast Feeding; Parity; Adult; Middle Aged; Pregnancy; Aged; Surveys and Questionnaires; Receptors, Progesterone
PubMed: 38812646
DOI: 10.55730/1300-0144.5784 -
Asian Pacific Journal of Cancer... May 2024Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell...
OBJECTIVE
Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell receptors like estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. This study aimed to identify, through bioinformatic analysis, the key genes associated with triple-negative breast cancer. In addition, CBD analogs with potential inhibitory effects on these genes were evaluated through docking and molecular dynamics.
METHODS
Gene expression profiles from the GSE178748 dataset were analyzed, focusing on MDA-MB-231 breast cancer cell lines. Differentially expressed genes were determined through protein-protein interaction networks and subsequently validated. Additionally, the inhibitory effects of cannabidiol analogs on these hub genes were assessed using molecular docking and dynamics.
RESULTS
Analysis of the hub highlighted RPL7A, NHP2L1, and PSMD11 as significant players in TNBC regulation. Ligand 44409296 showed the best affinity energy with RPL7A, while 166505341 exhibited the highest affinity with NHP2L1 and PSMD11, surpassing CBD. Analyses of RMSD, RMSF, SASA, and Gyration Radius indicated structural stability and interactions of the proteins with ligands over time. MMGBSA calculations showed favorable binding energies for the ligands with the target proteins.
CONCLUSION
In conclusion, this study identified key genes, namely RPL7A, NHP2L1, and PSMD11, associated with triple-negative breast cancer and demonstrated promising interactions with cannabidiol analogs, particularly 44409296 and 166505341. These findings suggest potential therapeutic targets and highlight the relevance of further clinical investigations. Additionally, the ligands exhibited favorable ADME properties and low toxicity, underscoring their potential in future drug development for TNBC treatment.
Topics: Triple Negative Breast Neoplasms; Humans; Cannabidiol; Female; Molecular Docking Simulation; Computational Biology; Computer Simulation; Gene Expression Regulation, Neoplastic; Protein Interaction Maps; Molecular Dynamics Simulation; Antineoplastic Agents; Cell Line, Tumor
PubMed: 38809637
DOI: 10.31557/APJCP.2024.25.5.1649 -
Open Veterinary Journal Apr 2024Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve...
BACKGROUND
Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve reproductive performance in dairy cows has become a necessity.
AIM
Improve reproductive performance and ovarian activity in postpartum cows with specific customized treatment for OC and PFs.
METHODS
The study included 48 cows at 14 days P.P, which received two dosages of 500 μg IM cloprostenol, 14 days apart as presynchronization protocol. Ultrasound ovarian scans 14 days after the last injection for 4 weeks. The cows were divided into three groups according to ovarian status: OC ( = 14), PF ( = 12), and NE ( = 22). In the OC group, received 500 μg IM cloprostenol and 100 μg IM cystoriline, a second dose of cloprostenol 14 days later and a second dose of cystoriline 36 hours later, and AI after 24 hours (GnRH+ PG/PG/GnRH). In the PF group, was fitted with progesterone-releasing intravaginal device (PRID) for 9 days; the same day, they received 100 μg cystoreline then 500 μg cloprostenol 7 days later, after PRID removal AI 56 hours later (PRID + GnRH/PG). In the NE group, artificial insemination was implemented until 28 days depending on estrus detection.
RESULTS
The ovarian activity was greatly affected by the customized treatments, leading to enhanced follicular and luteal activity, particularly after the PGF2α injection. The OC and PF groups showed substantial estrus responses of 71.43% and 75.02%, respectively, during AI time. While the NE group had an ovulation rate of 54.5% and a pregnancy rate of 31.8%, the treatment groups showed marked improvements in reproductive performance. The ovulation rates in the OC and PF groups were 71.43% and 75% and the pregnancy rates at the 1st artificial insemination were 64.28% and 66.7%.
CONCLUSION
Improving reproductive performance and minimizing the time to first service are possible advantages of early case-specific treatment for postpartum cows with OC and PFs.
Topics: Animals; Female; Cattle; Ovarian Cysts; Postpartum Period; Cloprostenol; Cattle Diseases; Insemination, Artificial; Pregnancy; Ovarian Follicle; Progesterone; Estrus Synchronization
PubMed: 38808298
DOI: 10.5455/OVJ.2024.v14.i4.10 -
Clinical Case Reports Jun 2024Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous...
KEY CLINICAL MESSAGE
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.
UNLABELLED
We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.
PubMed: 38808199
DOI: 10.1002/ccr3.9015 -
JAMA Network Open May 2024Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.
OBJECTIVES
To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024.
INTERVENTION
Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age.
MAIN OUTCOMES AND MEASURES
The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment.
RESULTS
The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02133573.
Topics: Humans; Progesterone; Female; Heart Defects, Congenital; Male; Pregnancy; Double-Blind Method; Infant; Adult; Infant, Newborn; Child Development; Progestins; Neurodevelopmental Disorders
PubMed: 38805228
DOI: 10.1001/jamanetworkopen.2024.12291 -
Journal of Xenobiotics May 2024Progesterone receptor membrane component 1 (PGRMC1) is one of few proteins that have been recently described as direct modulators of the activity of human cytochrome... (Review)
Review
Progesterone receptor membrane component 1 (PGRMC1) is one of few proteins that have been recently described as direct modulators of the activity of human cytochrome P450 enzymes (CYP)s. These enzymes form a superfamily of membrane-bound hemoproteins that metabolize a wide variety of physiological, dietary, environmental, and pharmacological compounds. Modulation of CYP activity impacts the detoxification of xenobiotics as well as endogenous pathways such as steroid and fatty acid metabolism, thus playing a central role in homeostasis. This review is focused on nine main topics that include the most relevant aspects of past and current PGRMC1 research, focusing on its role in CYP-mediated drug metabolism. Firstly, a general overview of the main aspects of xenobiotic metabolism is presented (I), followed by an overview of the role of the CYP enzymatic complex (IIa), a section on human disorders associated with defects in CYP enzyme complex activity (IIb), and a brief account of cytochrome (cyt )'s effect on CYP activity (IIc). Subsequently, we present a background overview of the history of the molecular characterization of PGRMC1 (III), regarding its structure, expression, and intracellular location (IIIa), and its heme-binding capability and dimerization (IIIb). The next section reflects the different effects PGRMC1 may have on CYP activity (IV), presenting a description of studies on the direct effects on CYP activity (IVa), and a summary of pathways in which PGRMC1's involvement may indirectly affect CYP activity (IVb). The last section of the review is focused on the current challenges of research on the effect of PGRMC1 on CYP activity (V), presenting some future perspectives of research in the field (VI).
PubMed: 38804287
DOI: 10.3390/jox14020034 -
Heliyon May 2024We describe vaginal microbiota, including species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm...
We describe vaginal microbiota, including species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB <34 weeks' gestation. Participants collected three vaginal swabs in the first and second trimester. Vaginal microbiota was profiled with 16S rDNA sequencing. species and STI's were tested with qPCR. Standard care was provided according to local protocol, including screening and treatment for bacterial vaginosis (BV), routine progesterone administration and screening for cervical length shortening. Of 154 participants, 26 (16.9 %) experienced recurrent sPTB <37 weeks' gestation. Microbiota composition was not associated with sPTB. During pregnancy, the share of dominated microbiota increased at the expense of diverse microbiota between the first and second trimester. This change coincided with treatment for BV, demonstrating a similar change in microbiota composition after treatment. In this cohort of high-risk women, we did not find an association between vaginal microbiota composition and recurrent sPTB. This should be interpreted with care, as these women were offered additional preventive therapies to reduce sPTB according to national guidelines including progesterone and BV treatment. The increase observed in dominated microbiota and the decrease in diverse microbiota mid-gestation was most likely mediated by BV treatment. Our findings suggest that in recurrent sPTB occurring despite several preventive therapies, the microbe-related etiologic contribution might be limited.
PubMed: 38803950
DOI: 10.1016/j.heliyon.2024.e30685 -
JBRA Assisted Reproduction May 2024Late follicular premature progesterone rise is a complex phenomenon encountered during assisted reproductive technology (ART) treatments; different etiologies can occur...
OBJECTIVE
Late follicular premature progesterone rise is a complex phenomenon encountered during assisted reproductive technology (ART) treatments; different etiologies can occur in the same patient. Low ovarian responders may be the best example, since higher FSH doses and ovarian aging-related changes may interact and generate a premature progesterone rise. This study aims to explore the correlation between progesterone levels on hCG day and the progesterone-to-follicle index and compare the progesterone-to-follicle index according to ovarian response.
METHODS
We performed a retrospective, observational, analytic, cross-sectional, and cohort study at the Reproductive Endocrinology Department at Centro Médico Nacional 20 de November between January 2015 to January 2020. After verifying for normalcy, a Spearman Rho, Principal Component Analysis, and a simple linear regression model were performed. Treatment cycles were classified according to their ovarian response. Low-ovarian responders were classified according to the Bologna Criteria. Then an ANOVA test was performed to compare each group.
RESULTS
Our results show that the progesterone-to-follicle index correlates best with progesterone levels on hCG day. Comparing all the ovarian responses, low ovarian responders have the highest progesterone-to-follicle index of the four groups.
CONCLUSIONS
Low ovarian responders produce more progesterone per follicle than regular and high responders.
PubMed: 38801316
DOI: 10.5935/1518-0557.20240043 -
Cureus May 2024Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by dyslipidemia, hormonal...
Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by dyslipidemia, hormonal imbalances, and metabolic dysfunctions. Vitamin D deficiency may be implicated in the pathogenesis of PCOS, potentially exacerbating its metabolic syndrome. However, the exact interplay between these factors remains underexplored. Aim This study aimed to evaluate serum levels of vitamin D and its association with modalities of PCOS among women with PCOS and healthy controls. Methods This was a hospital-based case-control study where 60 women newly diagnosed with PCOS and 56 non-PCOS controls were consecutively recruited within a 10-month period. The women aged 20-40 were recruited at the gynecology clinics of Lagos State University Teaching Hospital and Lagos Island Maternity Hospital. PCOS was diagnosed using the Rotterdam's criteria. The biodata, anthropometry, clinical features, serum vitamin D, cortisol, progesterone, testosterone, estradiol, prolactin, anti-Mullerian hormone (AMH), thyroid-stimulating hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin, fasting blood glucose (FBG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and very-low-density lipoprotein cholesterol (VLDL-C) levels of PCOS-diagnosed women were assessed and compared with those of women without PCOS. The exclusion criteria comprised known diabetics, women with gynecological pathologies such as fibroids, and women on medications affecting the study analytes or hormones. Statistical analyses included chi-square or Fisher's exact tests for categorical variables, student t-test for continuous variables, and Pearson's correlation for assessing relationships between continuous variables. The significance level was set at p<0.05 and a confidence interval of 95%. Results Individuals with PCOS exhibited a younger mean age (26.90±3.73 versus 29.95±5.00 years, p=0.001) and a higher prevalence of irregular menstrual patterns (46.7% versus 14.3%, p=0.0001) and acne (58.3% versus 37.5%, p=0.025). Moreover, PCOS was associated with elevated levels of TC (p = 0.03), TG (p = 0.03), LDL-C (p = 0.014), FBG (p = 0.001), LH:FSH ratio (p = 0.002), AMH (p = 0.0001), and testosterone (p = 0.003), but low progesterone (p = 0.001) and vitamin D (p = 0.033), alongside a higher incidence of vitamin D deficiency (33.3% versus 26.1%) and insufficiency (66.7% versus 56.5%). Additionally, significant but weak correlations were observed between serum vitamin D levels and waist-hip ratio (r = 0.4, p = 0.016) and FBG (r = -0.4, p = 0.036) in the PCOS group, suggesting potential metabolic implications. Conclusion The PCOS subjects in this study had decreased vitamin D and progesterone levels, with elevated concentrations of testosterone, AMH, lipid profile (TC, LDL, and TG), FBG, and LH:FSH ratio. Studies on the therapeutic effect of vitamin D administration in managing PCOS will need to be further evaluated.
PubMed: 38800769
DOI: 10.7759/cureus.60975